Effects of Perioperative Nesiritide or Milrinone Infusion on Recovery From Fontan Surgery

NCT ID: NCT00543309

Last Updated: 2018-06-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2013-07-31

Brief Summary

The staged surgical pathway to treat children with single ventricle heart defects culminates with the Fontan operation. In this procedure, systemic venous return is rerouted directly to the pulmonary arteries, which serves to separate the systemic and pulmonary circulations. Although mortality following the Fontan operation is now uncommon, early postoperative morbidity including prolonged postoperative chest tube drainage and hospitalization remains significant. The efficacy of empiric inotropic, vasodilator and neurohumoral-inhibitory therapies in the perioperative period is unknown and practice varies widely between centers.

The investigators will propose a single-center, randomized, double-blind, phase II clinical trial in children undergoing Fontan surgery. The investigators plan to compare the effects of perioperative nesiritide, milrinone and placebo infusions on the early postoperative clinical course and neurohumoral profile. The investigators hypothesize that, when compared to the milrinone and placebo groups, the nesiritide group will have more days alive and out of the hospital within the first 30 days after surgery.

Detailed Description

The staged surgical pathway to treat children with single ventricle heart defects culminates with the Fontan operation. In this procedure, systemic venous return is rerouted directly to the pulmonary arteries, which serves to separate the systemic and pulmonary circulations. Following this operation, deoxygenated blood flows passively from the body through the lungs without a pumping chamber. Although mortality following the Fontan operation is now uncommon, early postoperative morbidity including prolonged postoperative chest tube drainage and hospitalization remains significant. The efficacy of empiric inotropic, vasodilator and neurohumoral-inhibitory therapies in the perioperative period is unknown and practice varies widely between centers.

We propose a single-center, randomized, double-blind, phase II clinical trial in children undergoing Fontan surgery. We plan to compare the effects of perioperative nesiritide, milrinone and placebo infusions on the early postoperative clinical course and neurohumoral profile. The primary aim of the study is to determine whether nesiritide, milrinone or placebo infusion is associated with fewer days alive and out of the hospital within 30 days of surgery. We hypothesize that, when compared to the milrinone and placebo groups, the nesiritide group will have more days alive and out of the hospital within the first 30 days after surgery. Secondary aims are to determine the effects of these infusions on postoperative resource consumption, hemodynamics, arrhythmias, renal function, neurohumoral activation and adverse events. Thirty-nine patients per group (117 total patients) will be enrolled over three years.

Conditions

Heart Defects, Congenital

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

I- nesiritide

Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met.

Group Type: EXPERIMENTAL

nesiritide

Intervention Type: DRUG

Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted

II- Milrinone

Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met.

Group Type: ACTIVE_COMPARATOR

milrinone

Intervention Type: DRUG

Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted

III- placebo

Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Placebo bolus on CPB, then placebo infusion

Interventions

nesiritide

Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted

Intervention Type: DRUG

milrinone

Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted

Intervention Type: DRUG

placebo

Placebo bolus on CPB, then placebo infusion

Intervention Type: DRUG

Other Intervention Names

Natrecor; Primacor

Eligibility Criteria

Inclusion Criteria

• Patients undergoing an elective, primary Fontan operation at Children's Hospital Boston.

Exclusion Criteria

• Revision surgery for failing Fontan circulation.
• Preoperative serum creatinine > 1.5 mg/dL or chronic dialysis.
• The attending surgeon, cardiac anesthesiologist, or cardiac intensivist has a compelling indication to initiate either nesiritide or milrinone outside of the confines of the study.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Heart Association

OTHER

Sponsor Role: collaborator

John M Costello

OTHER

Sponsor Role: lead

Responsible Party

John M Costello

Associate in Cardiology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

John M Costello, MD MPH

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Locations

Children's Hospital Boston

Boston, Massachusetts, United States

Countries

United States

References

Costello JM, Dunbar-Masterson C, Allan CK, Gauvreau K, Newburger JW, McGowan FX Jr, Wessel DL, Mayer JE Jr, Salvin JW, Dionne RE, Laussen PC. Impact of empiric nesiritide or milrinone infusion on early postoperative recovery after Fontan surgery: a randomized, double-blind, placebo-controlled trial. Circ Heart Fail. 2014 Jul;7(4):596-604. doi: 10.1161/CIRCHEARTFAILURE.113.001312. Epub 2014 Jun 6.

Reference Type: RESULT

PMID: 24906491 (View on PubMed)

Other Identifiers

0735070N

Identifier Type: -

Identifier Source: org_study_id